Forkhead box M1 (FoxM1), a member of the Fox family of transcriptional factors, is involved in the development of various human malignancies. However, the expression level of FoxM1 and its functional role in hypopharyngeal squamous cell carcinoma (HSCC) remained unclear to date. The aim of the present study was to investigate the FoxM1 expression in 63 HSCC and 20 adjacent normal tissues, as well as to evaluate its association with the clinicopathological parameters and its diagnostic value in HSCC. To further explore the biological function of FoxM1 in vitro, siRNAs were used to knockdown the expression of FoxM1 in the HSCC cell line Fadu. The results revealed that FoxM1 protein was highly expressed in HSCC tissues and that its high expression was closely associated with HSCC tumor differentiation (P=0.004), tumor size (P=0.002), clinical stage (P=0.001), lymph node metastasis (P=0.002), treatment (P=0.045) and expression of the proliferation marker Ki-67 (P<0.001). Additionally, the elevated expression of FoxM1 in HSCC patients consistently predicted a poor survival time. Knockdown of FoxM1 expression blocked Fadu cell proliferation and promoted apoptosis, and also led to the down-regulation of cyclin A1 expression. Furthermore, decreased expression of FoxM1 markedly impeded cell migration and reversed the epithelial-mesenchymal transition phenotype, as indicated by decreased expression of vimentin and increased expression of E-cadherin in Fadu cells. These results indicate that FoxM1 may act as an oncogene and serve as a therapeutic target against malignant progression in HSCC.

Stathmin1, a microtubule-destabilizing phosphoprotein, is considered to play a crucial role in regulating cellular microtubule dynamics and controlling mitosis. Previous studies have showed that STMN1 is highly expressed in many human malignancies and is related to development, invasion and metastasis of tumors. However, its expression pattern, clinical performance and functional roles in hypopharyngeal squamous cell carcinoma (HSCC) have not been addressed. In this study, we found that STMN1 was significantly elevated in HSCC and its expression level was correlated with poor differentiation (P<0.001), clinical stage (P<0.001), large tumor size (P=0.001) and lymph node metastasis (P=0.008). A positive correlation between STMN1 and Ki-67 expression was also exhibited. High STMN1 expression predicted poor survival. Furthermore, we found that knockdown of STMN1 by siRNAs inhibited the FaDu cell proliferation and migration. Moreover, decreased STMN1 expression in FaDu cells reversed the acquisition of EMT phenotype by upregulating E-cadherin, as well as reduced vimentin expression at protein and mRNA levels. These results suggested that STMN1 plays an important role in proliferation and migration of HSCC and may be used as a potential prognostic biomarker or therapeutic target of HSCC.

The aim of this study was to determine the effect of A disintegrin and metalloprotease 10 (ADAM10) protein expression on the progression, migration and prognosis of hypopharyngeal squamous cell carcinoma (HSCC). Immunohistochemistry and western blot analysis were performed to detect ADAM10 expression in human HSCC specimens. Cell Counting Kit-8 (CCK-8) assay, flow cytometry analysis and wound-healing assay were employed to investigate the effects of ADAM10 knockdown (ADAM10-RNAi) on major oncogenic properties of FaDu cells. We detected that ADAM10 was overexpressed in HSCC specimens and its expression level was associated with differentiation (p<0.001), tumor size (p=0.019), lymph node metastasis (p=0.001), clinical stage (p<0.001), proliferation marker Ki-67 expression (P=0.001) and overall survival (p<0.046). ADAM10-RNAi in FaDu cells resulted in the inhibition of proliferation and the decrease in migration. Moreover, mechanistic experiments revealed that ADAM10-RNAi resulted in an increase in E-cadherin and a decrease in N-cadherin and vimentin expression. Our study implies that high expression of ADAM10 promotes the proliferation and migration of HSCC. These findings may help to provide a method for treatment of HSCC.

Perfluorooctane sulfonate (PFOS), a kind of organic pollutant widely found in the environment and biota, could alter normal brain development and produce cognitive dysfunction. For the past years, the neurotoxic effects of PFOS have been shown. Recent studies have proven that PFOS can induce neuronal apoptosis and cause neurotoxicity, but the regulatory proteins referred to the process have not been clarified. In this study, PC12 cells were used to investigate the changes of the expression of apoptosis-related proteins, forkhead box O3 (FoxO3a) and pro-apoptotic Bcl-2 proteins. We detected that the levels of cleaved caspase-3 and cleaved PARP were up-regulated obviously in PFOS-treated PC12 cells by using Western blotting, and that the apoptotic rate of PC12 cells was increased significantly by using flow cytometry, verifying that PFOS could induce neuronal apoptosis. Western blot analysis and immunofluorescence revealed obvious up-regulation of the expression of FoxO3a and proapoptotic Bcl-2 proteins. In addition, knockdown of FoxO3a gene inhibited Bim expression and apoptosis. According to the data, we believe that FoxO3a may play a crucial role in PFOS-induced neurotoxicity.